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Microglia are resident immune cells in the central nervous system that are rapidly activated to mediate neuroinflammation and apoptosis, thereby aggravating brain tissue damage after ischemic stroke (IS). Although scutellarin has a specific therapeutic effect on IS, the potential target mechanism of its treatment has not been fully elucidated. In this study, we explored the potential mechanism of scutellarin in treating IS using network pharmacology. Lipopolysaccharide (LPS) was used to induce an in vitro BV-2 microglial cell model, while middle cerebral artery occlusion (MCAO) was used to induce an in vivo animal model. Our findings indicated that scutellarin promoted the recovery of cerebral blood flow in MCAO rats at 3 days, significantly different from that in the MCAO group. Western blotting and immunofluorescence revealed that scutellarin treatment of BV-2 microglial cells resulted in a significant reduction in the protein expression levels and incidence of cells immunopositive for p-NF-κB, TNF-α, IL-1ß, Bax, and C-caspase-3. In contrast, the expression levels of p-PI3K, p-AKT, p-GSK3ß, and Bcl-2 were further increased, significantly different from those in the LPS group. The PI3K inhibitor LY294002 had similar effects to scutellarin by inhibiting neuroinflammation and apoptosis in activated microglia. The results of the PI3K/AKT/GSK3ß signaling pathway and NF-κB pathway in vivo in MCAO models induced microglia at 3 days were consistent with those obtained from in vitro cells. These findings indicate that scutellarin plays a neuroprotective role by reducing microglial neuroinflammation and apoptosis mediated by the activated PI3K/AKT/GSK3ß/NF-κB signaling pathway.
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Background: The isolated systolic hypertension (ISH) is of high prevalence, with a relatively poor prognosis. However, there is still no direct evidence to demonstrate the benefits of intensive blood pressure (BP) control among these patients. We aimed to evaluate intensive BP control with the target of <130/80 mmHg in ISH. Methods: This was a post hoc analysis of patients with ISH in the China Rural Hypertension Control Project (CRHCP), defined as systolic blood pressure (SBP) ≥ 140 mmHg and diastolic blood pressure (DBP) < 90 mmHg. The primary outcome was cardiovascular disease (CVD) including stroke, myocardial infarction, heart failure, and CVD death. Mixed-effect Cox proportional regression and generalized estimating equation models were used for analysis. Findings: In total, 7981 patients were randomly assigned to the intervention group and 8005 to the usual care group between May 8 and November 27, 2018. The median follow-up was 3.02 years (25-75%: 2.98-3.06). Mean systolic/diastolic BP at the end of 36 months follow-up was 126.5/71.2 mmHg in the intensive BP control group and 148.1/78.6 mmHg in the usual care group. The intervention group presented a substantially lower rate of composite CVD compared with the usual care group (1.52% versus 2.30%/year; multiple-adjusted hazard ratio (HR): 0.64; 95% confidence interval (CI): 0.57-0.72; P < 0.001), especially for stroke (multiple-adjusted HR: 0.61; 95% CI: 0.53-0.70; P < 0.001), HF (multiple-adjusted HR: 0.57; 95% CI: 0.36-0.91; P = 0.017) and CVD death (multiple-adjusted HR: 0.64; 95% CI: 0.50-0.83; P < 0.001). The primary composite outcome was substantially reduced by 36% in the intervention group compared with the usual care group. The further interaction analysis revealed that the reduction of primary outcome by intervention was consistent across subgroups of sex, age, education level, history of CVD, use of antihypertensive medication and baseline DBP (P > 0.05 for all interaction test). The incidences of symptomatic hypotension, syncope injurious falls and renal outcomes did not differ between the two groups, even though hypotension was increased in intervention group (RR:1.71; 95% CI: 1.28-2.28; P < 0.001). Interpretation: Intensive BP control (<130/80 mmHg) was effective and safe in patients with ISH for the prevention of CVD events. Funding: The Ministry of Science and Technology (China) of China and the Science and Technology Program of Liaoning Province, China.
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Aims/Background Rosuvastatin is a common lipid-lowering statin on the market, but its impact on the incidence of long-term cardiovascular events is not well clarified. This study aimed to explore the effects of rosuvastatin on serum asymmetric dimethylarginine (ADMA) levels and the incidence of long-term cardiovascular events in patients with hyperlipidaemia and H-type hypertension. Methods This retrospective study included 158 patients with hyperlipidaemia and H-type hypertension who were treated in the Hebei Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine from August 2015 to August 2016. The patients were divided into an occurrence group and a non-occurrence group according to the occurrence of long-term cardiovascular events following the resuvostatin treatment. The changes in blood lipids, blood pressure, serum ADMA levels and vascular endothelial function indexes before and after treatment were compared, and the effect of ADMA on the occurrence of long-term cardiovascular events and its predictive efficacy were analysed using the Spearman correlation test and receiver operating characteristics (ROC) curve. Results After treatment, the levels of serum total cholesterol, low-density lipoprotein cholesterol, triglyceride, serum ADMA and blood pressure became significantly lower (p < 0.001), with high-density lipoprotein cholesterol exhibiting no significant difference. Twenty-two cases developed long-term cardiovascular events after the treatment, with an incidence of 13.92%. The occurrence group had significantly higher serum ADMA levels than the non-occurrence group (p < 0.001). The rosuvastatin treatment also lowered the levels of endothelin-1 and high-sensitivity C-reactive protein and increased the nitric oxide level (p < 0.001). Spearman correlation analysis showed that serum ADMA levels were positively correlated with the occurrence of long-term cardiovascular events (r=0.462, p < 0.001). Meanwhile, according to the ROC curve, serum ADMA had a good predictive efficacy for long-term cardiovascular events, with an area under the curve of 0.885 (95% confidence interval 0.808-0.963; p < 0.001). Conclusion Rosuvastatin can reduce ADMA levels and exert vascular protective effects. The increase in serum ADMA levels is closely related to the occurrence of long-term cardiovascular events in patients with hyperlipidaemia and H-type hypertension, serving as a potential clinical predictor to guide disease prevention and treatment.
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Arginina , Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipidemias , Hipertensão , Rosuvastatina Cálcica , Humanos , Arginina/análogos & derivados , Arginina/sangue , Rosuvastatina Cálcica/uso terapêutico , Masculino , Feminino , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/sangue , Hiperlipidemias/epidemiologia , Hiperlipidemias/complicações , Pessoa de Meia-Idade , Estudos Retrospectivos , Hipertensão/tratamento farmacológico , Hipertensão/sangue , Hipertensão/epidemiologia , Hipertensão/complicações , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Idoso , Incidência , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/sangue , Pressão Sanguínea/efeitos dos fármacosRESUMO
New energy sources are transforming the automotive market. This shift has also expanded the possibilities for in-vehicle interaction. Through a literature review, this study categorizes the in-vehicle interaction activities into three types: driving tasks, comfort tasks, and entertainment tasks. This study conducted empirical survey of 377 users to understand their preferences of in-vehicle interaction input methods inside new energy vehicles. The results show that gender, educational level, income, driver's license type and driving experience have significant influence on the perception and preference of the in-vehicle interaction input methods. However, age and experience with new energy vehicle didn't show significant results. The findings of this study can assist manufacturers in developing targeted solutions and meeting the personalized needs of users in future vehicle market segments.
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BACKGROUND: The 2018/2023 ESC/ESH Guidelines underlined a gap how baseline cardiovascular disease (CVD) risk predicted blood pressure (BP) lowering benefits. Further, 2017 ACC/AHA Guideline and 2021 WHO Guideline recommended implementation studies about intensive BP control. Now, to bridge these guideline gaps, we conducted a post hoc analysis to validate whether the baseline CVD risk influences the effectiveness of the intensive BP control strategy, which was designed by China Rural Hypertension Control Project (CRHCP). METHODS: This is a post hoc analysis of CRHCP, among which participants were enrolled except those having CVD history, over 80 years old, or missing data. Subjects were stratified into quartiles by baseline estimated CVD risk and then grouped into intervention and usual care group according to original assignment in CRHCP. Participants in the intervention group received an integrated, multi-faceted treatment strategy, executed by trained non-physician community health-care providers, aiming to achieve a BP target of < 130/80 mmHg. Cox proportional-hazards models were used to estimate the hazard ratios of outcomes for intervention in each quartile, while interaction effect between intervention and estimated CVD risk quartiles was additionally assessed. The primary outcome comprised myocardial infarction, stroke, hospitalization for heart failure, or CVD deaths. RESULTS: Significant lower rates of primary outcomes for intervention group compared with usual care for each estimated CVD risk quartile were reported. The hazard ratios (95% confidence interval) in the four quartiles (from Q1 to Q4) were 0.59 (0.40, 0.87), 0.54 (0.40, 0.72), 0.72 (0.57, 0.91) and 0.65 (0.53, 0.80), respectively (all Ps < 0.01). There's no significant difference of hazard ratios by intervention across risk quartiles (P for interaction = 0.370). Only the relative risk of hypotension, not symptomatic hypotension, was elevated in the intervention group among upper three quartiles. CONCLUSIONS: Intensive BP lowering strategy designed by CRHCP group was effective and safe in preventing cardiovascular events independent of baseline CVD risk. TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov, NCT03527719.
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Doenças Cardiovasculares , Hipertensão , Humanos , Masculino , Feminino , China/epidemiologia , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Pessoa de Meia-Idade , Idoso , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/epidemiologia , Pressão Sanguínea/fisiologia , População Rural , Anti-Hipertensivos/uso terapêutico , Resultado do Tratamento , Fatores de Risco de Doenças CardíacasRESUMO
In this paper, we present a study of the thermal transport of epitaxial bilayer graphene microbridges. The thermal conductance of three graphene microbridges with different lengths was measured at different temperatures using Johnson noise thermometry. We find that with the decrease of the temperature, the thermal transport in the graphene microbridges switches from electron-phonon coupling to electron diffusion, and the switching temperature is dependent on the length of the microbridge, which is in good agreement with the simulation based on a distributed hot-spot model. Moreover, the electron-phonon thermal conductance has a temperature power law of T3 as predicted for pristine graphene and the electron-phonon coupling coefficient σep is found to be approximately 0.18 W/(m2 K4), corresponding to a deformation potential D of 55 eV. In addition, the electron diffusion in the graphene microbridges adheres to the Wiedemann-Franz law, requiring no corrections to the Lorentz number.
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Importance: The sustainable effectiveness and safety of a nonphysician community health care practitioner-led intensive blood pressure intervention on cardiovascular disease have not, to the authors' knowledge, been studied, especially in the older adult population. Objective: To evaluate such a multifaceted model with a more stringent blood pressure treatment goal (<130/80 mm Hg) among patients aged 60 years and older with hypertension. Design, Setting, and Participants: This was a 48-month follow-up study of the China Rural Hypertension Control Project (CRHCP), an open-cluster randomized clinical trial, conducted from 2018 to 2023. Participants 60 years and older and younger than 60 years with a diagnosis of hypertension from the CRHCP trial were included for analysis. Individuals were recruited from 326 villages in rural China. Interventions: The well-trained, nonphysician, community health care practitioner implemented a multifaceted intervention program (eg, initiation or titration of antihypertensive medications) to achieve a blood pressure level of less than 130/80 mm Hg, supervised by primary care physicians. Main Outcomes and Measures: Cardiovascular disease (a composite of myocardial infarction, stroke, heart failure requiring hospitalization, and cardiovascular disease death). Results: A total of 22â¯386 individuals 60 years and older with hypertension and 11â¯609 individuals younger than 60 years with hypertension were included in the analysis. The mean (SD) age of the participants was 63.0 (9.0) years and included 20â¯825 females (61.3%). Among the older individuals with hypertension, a total of 11â¯289 patients were randomly assigned to the intervention group and 11â¯097 to the usual-care group. During a median (IQR) of 4.0 (4.0-4.1) years, there was a significantly lower rate of total cardiovascular disease (1133 [2.7%] vs 1433 [3.5%] per year; hazard ratio [HR], 0.75; 95% CI, 0.69-0.81; P < .001) and all-cause mortality (1111 [2.5%] vs 1210 [2.8%] per year; HR, 0.90; 95% CI, 0.83-0.98; P = .01) in the intervention group than in the usual-care group. For patients younger than 60 years, the risk reductions were also significant for total cardiovascular disease (HR, 0.64; 95% CI, 0.56-0.75; P < .001), stroke (HR, 0.64; 95% CI, 0.55-0.76; P < .001), heart failure (HR, 0.39; 95% CI, 0.18-0.87; P = .02), and cardiovascular death (HR, 0.54; 95% CI, 0.37-0.77; P < .001), with all interaction P values for age groups greater than .05. In both age categories, the incidences of injurious falls, symptomatic hypotension, syncope, and the results for kidney outcomes did not differ significantly between groups. Conclusions and Relevance: In both the aging and younger general population with hypertension, the nonphysician health care practitioner-led, multifaceted, intensive blood pressure intervention model could effectively and safely reduce the risk of cardiovascular disease and all-cause death. Trial Registration: ClinicalTrials.gov Identifier: NCT03527719.
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Ciliophora, an exceptionally diverse lineage of unicellular eukaryotes, exhibits a remarkable range of species richness across classes in the ciliate Tree of Life. In this study, we have acquired transcriptome and genome data from 40 representative species in seven ciliate classes. Utilizing 247 genes and 105 taxa, we devised a comprehensive phylogenomic tree for Ciliophora, encompassing over 60 % of orders and constituting the most extensive dataset of ciliate species to date. We established a robust phylogenetic framework that encompasses ambiguous taxa and the major classes within the phylum. Our findings support the monophyly of each of two subphyla (Postciliodesmatophora and Intramacronucleata), along with three subclades (Protocruzia, CONTHREEP, and SAPML) nested within Intramacronucleata, and elucidate evolutionary positions among the major classes within the phylum. Drawing on the robust ciliate Tree of Life and three constraints, we estimated the radiation of Ciliophora around 1175 Ma during the middle of the Proterozoic Eon, and most of the ciliate classes diverged from their sister lineage during the latter half of this period. Additionally, based on the time-calibrated tree and species richness pattern, we investigated net diversification rates of Ciliophora and its classes. The global net diversification rate for Ciliophora was estimated at 0.004979 species/Ma. Heterogeneity in net diversification rates was evident at the class level, with faster rates observed in Oligohymenophorea and Spirotrichea than other classes within the subclades CONTHREEP and SAPML, respectively. Notably, our analysis suggests that variations in net diversification rates, rather than clade ages, appear to contribute to the differences in species richness in Ciliophora at the class level.
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Cilióforos , Filogenia , Cilióforos/genética , Cilióforos/classificação , Transcriptoma , Evolução Molecular , Especiação GenéticaRESUMO
Understanding the relationship between plant diversity and invasibility is essential in invasion ecology. Species-rich communities are hypothesized to be more resistant to invasions than species-poor communities. However, while soil microorganisms play a crucial role in regulating this diversity-invasibility relationship, the effects of plant competition mode and soil nutrient status on their role remain unclear. To address this, we conducted a two-stage greenhouse experiment. Soils were first conditioned by growing nine native species separately in them for 1 year, then mixed in various configurations with soils conditioned using one, three, or six species, respectively. Next, we inoculated the mixed soil into sterilized substrate soil and planted the alien species Rhus typhina and native species Ailanthus altissima as test plants. We set up two competition modes (intraspecific and interspecific) and two nutrient levels (fertilization using slow-release fertilizer and nonfertilization). Under intraspecific competition, regardless of fertilization, the biomass of the alien species was higher in soil conditioned by six native species. By contrast, under interspecific competition, the biomass increased without fertilization but remained stable with fertilization in soil conditioned by six native species. Analysis of soil microbes suggests that pathogens and symbiotic fungi in diverse plant communities influenced R. typhina growth, which varied with competition mode and nutrient status. Our findings suggest that the soil microbiome is pivotal in mediating the diversity-invasibility relationship, and this influence varies according to competition mode and nutrient status.
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Cyanobacteria are the oldest prokaryotic photoautotrophic microorganisms and have evolved complicated post-translational modification (PTM) machinery to respond to environmental stress. Lysine 2-hydroxyisobutyrylation (Khib) is a newly identified PTM that is reported to play important roles in diverse biological processes, however, its distribution and function in cyanobacteria have not been reported. Here, we performed the first systematic studies of Khib in a model cyanobacterium Synechococcus sp. strain PCC 7002 (Syn7002) using peptide prefractionation, pan-Khib antibody enrichment, and high-accuracy mass spectrometry (MS) analysis. A total of 1875 high-confidence Khib sites on 618 proteins were identified, and a large proportion of Khib sites are present on proteins in the cellular metabolism, protein synthesis, and photosynthesis pathways. Using site-directed mutagenesis and functional studies, we showed that Khib of glutaredoxin (Grx) affects the efficiency of the PS II reaction center and H2O2 resistance in Syn7002. Together, this study provides novel insights into the functions of Khib in cyanobacteria and suggests that reversible Khib may influence the stress response and photosynthesis in both cyanobacteria and plants.
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Lisina , Processamento de Proteína Pós-Traducional , Synechococcus , Lisina/metabolismo , Synechococcus/metabolismo , Synechococcus/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Peróxido de Hidrogênio/metabolismo , Glutarredoxinas/metabolismo , Glutarredoxinas/genética , Complexo de Proteína do Fotossistema II/metabolismo , Complexo de Proteína do Fotossistema II/genética , Mutagênese Sítio-Dirigida , Fotossíntese , Cianobactérias/metabolismo , Cianobactérias/genética , Espectrometria de MassasRESUMO
Biomethylation is an effective means of arsenic detoxification by organisms living in aquatic environments. Ciliated protozoa (including Tetrahymena species) play an important role in the biochemical cycles of aquatic ecosystems and have a potential application in arsenic biotransformation. This study compared arsenic tolerance, accumulation, methylation, and efflux in 11 Tetrahymena species. Nineteen arsenite (As(III)) S-adenosylmethionine (SAM) methyltransferase (arsM) genes, of which 12 are new discoveries, were identified, and protein sequences were studied. We then constructed recombinant cell lines based on the Tetrahymena thermophila (T. thermophila) wild-type SB210 strain and expressed each of the 19 arsM genes under the control of the metal-responsive the MTT1 promoter. In the presence of Cd2+ and As(V), expression of the arsM genes in the recombinant cell lines was much higher than in the donor species. Evaluation of the recombinant cell line identified one with ultra-high arsenic methylation enzyme activity, significantly higher arsenic methylation capacity and much faster methylation rate than other reported arsenic methylated organisms, which methylated 89% of arsenic within 6.5â¯h. It also had an excellent capacity for the arsenic detoxification of lake water containing As(V), 56% of arsenic was methylated at 250⯵g/L As(V) in 48â¯h. This study has made a significant contribution to our knowledge on arsenic metabolism in protozoa and demonstrates the great potential to use Tetrahymena species in the arsenic biotransformation of aquatic environments.
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Arsênio , Tetrahymena thermophila , Arsênio/metabolismo , Ecossistema , Metilação , Metiltransferases/genética , Metiltransferases/metabolismo , Biotransformação , Tetrahymena thermophila/genética , Tetrahymena thermophila/metabolismoRESUMO
Mating type (sex) plays a crucial role in regulating sexual reproduction in most extant eukaryotes. One of the functions of mating types is ensuring self-incompatibility to some extent, thereby promoting genetic diversity. However, heterothallic mating is not always the best mating strategy. For example, in low-density populations or specific environments, such as parasitic ones, species may need to increase the ratio of potential mating partners. Consequently, many species allow homothallic selfing (i.e., self-fertility or intraclonal mating). Throughout the extensive evolutionary history of species, changes in environmental conditions have influenced mating strategies back and forth. However, the mechanisms through which mating-type recognition regulates sexual reproduction and the dynamics of mating strategy throughout evolution remain poorly understood. In this study, we show that the Cip1 protein is responsible for coupling sexual reproduction initiation to mating-type recognition in the protozoal eukaryote Tetrahymena thermophila. Deletion of the Cip1 protein leads to the loss of the selfing-avoidance function of mating-type recognition, resulting in selfing without mating-type recognition. Further experiments revealed that Cip1 is a regulatory subunit of the Cdk19-Cyc9 complex, which controls the initiation of sexual reproduction. These results reveal a mechanism that regulates the choice between mating and selfing. This mechanism also contributes to the debate about the ancestral state of sexual reproduction.
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Fertilidade , Reprodução , Reprodução/genética , Eucariotos/genética , Genes Fúngicos Tipo AcasalamentoRESUMO
Balantidium ctenopharyngodoni is identified as the sole ciliate species that exclusively resides within the hindgut of grass carp with high prevalence and intensity. In this study, the successful cultivation of B. ctenopharyngodoni enabled us to collect enough cells for genome sequencing. Consequently, we acquired a high-quality genome assembly spanning 68.66 Mb, encompassing a total of 22,334 nanochromosomes. Furthermore, we predicted 29,348 protein-coding genes, and 95.5% of them was supported by the RNA-seq data. The trend of GC content in the subtelomeric regions of single-gene chromosomes was similar to other ciliates containing nanochromosomes. A large number of genes encoding carbohydrate-binding modules with affinities for starch and peptidoglycans was identified. The identification of mitochondrion-related organelles (MROs) within genome indicates its well-suited adaptation to the anaerobic conditions in the hindgut environment. In summary, our results will offer resources for understanding the genetic basis and molecular adaptations of balantidia to hindgut of herbivorous fish.
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Balantidium , Genoma de Protozoário , Animais , Balantidium/genética , Sequência de Bases , Cromossomos , Filogenia , CarpasRESUMO
Lactococcus garvieae (L. garvieae) is a pathogenic bacterium that is Gram-positive and catalase-negative (GPCN), and it is capable of growing in a wide range of environmental conditions. This bacterium is associated with significant mortality and losses in fisheries, and there are concerns regarding its potential as a zoonotic pathogen, given its presence in cattle and dairy products. While we have identified and characterized virulent strains of L. garvieae through phenotyping and molecular typing studies, their impact on mammary tissue remains unknown. This study aims to investigate the pathogenicity of strong and weak virulent strains of L. garvieae using in vivo mouse models. We aim to establish MAC-T cell model to examine potential injury caused by the strong virulent strain LG41 through the TLR2/NLRP3/NF-kB pathway. Furthermore, we assess the involvement of NLRP3 inflammasome-mediated pyroptosis in dairy mastitis by silencing NLRP3. The outcomes of this study will yield crucial theoretical insights into the potential mechanisms involved in mastitis in cows caused by the L. garvieae-induced inflammatory response in MAC-T cells.
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Inflamassomos , Mastite , Humanos , Feminino , Animais , Bovinos , Camundongos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose , Linfócitos T/metabolismo , Lactococcus/metabolismo , Mastite/microbiologia , Mastite/veterinária , InflamaçãoRESUMO
Nonribosomal peptide synthetases (NRPSs) are large multidomain enzymes for the synthesis of a variety of bioactive peptides in a modular and pipelined fashion. Here, we investigated how the condensation (C) domain and the adenylation (A) domain cooperate with each other for the efficient catalytic activity in microcystin NRPS modules. We solved two crystal structures of the microcystin NRPS modules, representing two different conformations in the NRPS catalytic cycle. Our data reveal that the dynamic interaction between the C and the A domains in these modules is mediated by the conserved "RXGR" motif, and this interaction is important for the adenylation activity. Furthermore, the "RXGR" motif-mediated dynamic interaction and its functional regulation are prevalent in different NRPSs modules possessing both the A and the C domains. This study provides new insights into the catalytic mechanism of NRPSs and their engineering strategy for synthetic peptides with different structures and properties.
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Microcistinas , Peptídeo Sintases , Peptídeo Sintases/química , Conformação Molecular , PeptídeosRESUMO
As an emerging business model, merchants are selling surplus food in blind boxes, which provides new opportunities for reducing waste and promoting sustainable development. Surplus food blind boxes, however, have not been extensively researched in terms of design and marketing strategies. Therefore, we are examining how to increase consumers' purchase intention regarding surplus food blind boxes as well as the relationship between purchase intention, continuous intention, and recommendation intention. In this paper, two studies are conducted. As part of study 1, We used factor analysis to explore the reasons that influence consumers to purchase. In study 2, we utilized structural equation modeling to examine the impact of purchase intention on continuous intention and recommendation intention. Results indicate that food quality, perceived sustainability, and conspicuous consumption are the most important positive factors. The most important negative factors are perceived food risk, resistance to sales techniques, taste anxiety, and inadequate marketing strategies. Based on our findings, we constructed a path relationship between purchase intention, continuous intention, and recommendation intention. The purchase intention of the surplus food blind box users directly influences the recommendation intention and the continuous intention, while the recommendation intention indirectly influences the continuous intention. This study did not demonstrate that gender had a moderating effect. Meanwhile, it provides a reference for the actual marketing management of surplus food blind box merchants.
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Comportamento do Consumidor , Intenção , Humanos , Inquéritos e QuestionáriosRESUMO
Although most species have two sexes, multisexual (or multi-mating type) species are also widespread. However, it is unclear how mating-type recognition is achieved at the molecular level in multisexual species. The unicellular ciliate Tetrahymena thermophila has seven mating types, which are determined by the MTA and MTB proteins. In this study, we found that both proteins are essential for cells to send or receive complete mating-type information, and transmission of the mating-type signal requires both proteins to be expressed in the same cell. We found that MTA and MTB form a mating-type recognition complex that localizes to the plasma membrane, but not to the cilia. Stimulation experiments showed that the mating-type-specific regions of MTA and MTB mediate both self- and non-self-recognition, indicating that T. thermophila uses a dual approach to achieve mating-type recognition. Our results suggest that MTA and MTB form an elaborate multifunctional protein complex that can identify cells of both self and non-self mating types in order to inhibit or activate mating, respectively.
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Comunicação Celular , Reprodução , Membrana Celular , Cílios , Reconhecimento PsicológicoRESUMO
The Tibetan Plateau supplies water to nearly 2 billion people in Asia, but climate change poses threats to its aquatic microbial resources. Here, we construct the Tibetan Plateau Microbial Catalog by sequencing 498 metagenomes from six water ecosystems (saline lakes, freshwater lakes, rivers, hot springs, wetlands and glaciers). Our catalog expands knowledge of regional genomic diversity by presenting 32,355 metagenome-assembled genomes that de-replicated into 10,723 representative genome-based species, of which 88% were unannotated. The catalog contains nearly 300 million non-redundant gene clusters, of which 15% novel, and 73,864 biosynthetic gene clusters, of which 50% novel, thus expanding known functional diversity. Using these data, we investigate the Tibetan Plateau aquatic microbiome's biogeography along a distance of 2,500 km and >5 km in altitude. Microbial compositional similarity and the shared gene count with the Tibetan Plateau microbiome decline along with distance and altitude difference, suggesting a dispersal pattern. The Tibetan Plateau Microbial Catalog stands as a substantial repository for high-altitude aquatic microbiome resources, providing potential for discovering novel lineages and functions, and bridging knowledge gaps in microbiome biogeography.
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Microbiota , Humanos , Tibet , Microbiota/genética , Lagos , Rios , ÁguaRESUMO
The peptidyl-prolyl cis-trans isomerase Pin1 is a pivotal therapeutic target in cancers, but the regulation of Pin1 protein stability is largely unknown. High Pin1 expression is associated with SUMO1-modified protein hypersumoylation in glioma stem cells (GSCs), but the underlying mechanisms remain elusive. Here we demonstrate that Pin1 is deubiquitinated and stabilized by USP34, which promotes isomerization of the sole SUMO E2 enzyme Ubc9, leading to SUMO1-modified hypersumoylation to support GSC maintenance. Pin1 interacts with USP34, a deubiquitinase with preferential expression and oncogenic function in GSCs. Such interaction is facilitated by Plk1-mediated phosphorylation of Pin1. Disruption of USP34 or inhibition of Plk1 promotes poly-ubiquitination and degradation of Pin1. Furthermore, Pin1 isomerizes Ubc9 to upregulate Ubc9 thioester formation with SUMO1, which requires CDK1-mediated phosphorylation of Ubc9. Combined inhibition of Pin1 and CDK1 with sulfopin and RO3306 most effectively suppresses orthotopic tumor growth. Our findings provide multiple molecular targets to induce Pin1 degradation and suppress hypersumoylation for cancer treatment.